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#include <stdio.h>
#include <ctype.h>
#include <stdlib.h>
#include <string.h>
#include "clustalw.h"
/*
* Prototypes
*/
void calc_p_penalties(char **aln, sint n, sint fs, sint ls, sint *weight);
void calc_h_penalties(char **aln, sint n, sint fs, sint ls, sint *weight);
void calc_v_penalties(char **aln, sint n, sint fs, sint ls, sint *weight);
sint local_penalty(sint penalty, sint n, sint *pweight, sint *hweight, sint *vweight);
float percentid(char *s1, char *s2,sint length);
/*
* Global variables
*/
extern sint gap_dist;
extern sint max_aa;
extern sint debug;
extern Boolean dnaflag;
extern Boolean use_endgaps;
extern Boolean endgappenalties;
extern Boolean no_var_penalties, no_hyd_penalties, no_pref_penalties;
extern char hyd_residues[];
extern char *amino_acid_codes;
/* vwindow is the number of residues used for a window for the variable zone penalties */
/* vll is the lower limit for the variable zone penalties (vll < pen < 1.0) */
int vll=50;
int vwindow=5;
sint vlut[26][26] = {
/* A B C D E F G H I J K L M N O P Q R S T U V W X Y Z */
/*A*/ 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*B*/ 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*C*/ 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*D*/ 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*E*/ 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*F*/ 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*G*/ 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*H*/ 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*I*/ 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*J*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*K*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*L*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*M*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*N*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*O*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*P*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*Q*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0, 0,
/*R*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0, 0,
/*S*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0, 0,
/*T*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0, 0,
/*U*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 0,
/*V*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0, 0,
/*W*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0, 0,
/*X*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0,
/*Y*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1, 0,
/*Z*/ 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 1
};
/* pascarella probabilities for opening a gap at specific residues */
char pr[] = {'A' , 'C', 'D', 'E', 'F', 'G', 'H', 'K', 'I', 'L',
'M' , 'N', 'P', 'Q', 'R', 'S', 'T', 'V', 'Y', 'W'};
sint pas_op[] = { 87, 87,104, 69, 80,139,100,104, 68, 79,
71,137,126, 93,128,124,111, 75,100, 77};
sint pas_op2[] ={ 88, 57,111, 98, 75,126, 95, 97, 70, 90,
60,122,110,107, 91,125,124, 81,106, 88};
sint pal_op[] = { 84, 69,128, 78, 88,176, 53, 95, 55, 49,
52,148,147,100, 91,129,105, 51,128, 88};
float reduced_gap = 1.0;
Boolean nvar_pen,nhyd_pen,npref_pen; /* local copies of ho_hyd_penalties, no_pref_penalties */
sint gdist; /* local copy of gap_dist */
void calc_gap_coeff(char **alignment, sint *gaps, sint **profile, Boolean struct_penalties,
char *gap_penalty_mask, sint first_seq, sint last_seq,
sint prf_length, sint gapcoef, sint lencoef)
{
char c;
sint i, j;
sint is, ie;
static sint numseq,val,pcid;
static sint *gap_pos;
static sint *v_weight, *p_weight, *h_weight;
static float scale;
numseq = last_seq - first_seq;
if(numseq == 2)
{
pcid=percentid(alignment[first_seq],alignment[first_seq+1],prf_length);
}
else pcid=0;
for (j=0; j<prf_length; j++)
gaps[j] = 0;
/*
Check for a gap penalty mask
*/
if (struct_penalties != NONE)
{
nvar_pen = nhyd_pen = npref_pen = TRUE;
gdist = 0;
}
else if (no_var_penalties == FALSE && pcid > 60)
{
if(debug>0) fprintf(stderr,"Using variable zones to set gap penalties (pcid = %d)\n",pcid);
nhyd_pen = npref_pen = TRUE;
nvar_pen = FALSE;
}
else
{
nvar_pen = TRUE;
nhyd_pen = no_hyd_penalties;
npref_pen = no_pref_penalties;
gdist = gap_dist;
}
for (i=first_seq; i<last_seq; i++)
{
/*
Include end gaps as gaps ?
*/
is = 0;
ie = prf_length;
if (use_endgaps == FALSE && endgappenalties==FALSE)
{
for (j=0; j<prf_length; j++)
{
c = alignment[i][j];
if ((c < 0) || (c > max_aa))
is++;
else
break;
}
for (j=prf_length-1; j>=0; j--)
{
c = alignment[i][j];
if ((c < 0) || (c > max_aa))
ie--;
else
break;
}
}
for (j=is; j<ie; j++)
{
if ((alignment[i][j] < 0) || (alignment[i][j] > max_aa))
gaps[j]++;
}
}
if ((!dnaflag) && (nvar_pen == FALSE))
{
v_weight = (sint *) ckalloc( (prf_length+2) * sizeof (sint) );
calc_v_penalties(alignment, prf_length, first_seq, last_seq, v_weight);
}
if ((!dnaflag) && (npref_pen == FALSE))
{
p_weight = (sint *) ckalloc( (prf_length+2) * sizeof (sint) );
calc_p_penalties(alignment, prf_length, first_seq, last_seq, p_weight);
}
if ((!dnaflag) && (nhyd_pen == FALSE))
{
h_weight = (sint *) ckalloc( (prf_length+2) * sizeof (sint) );
calc_h_penalties(alignment, prf_length, first_seq, last_seq, h_weight);
}
gap_pos = (sint *) ckalloc( (prf_length+2) * sizeof (sint) );
/*
mark the residues close to an existing gap (set gaps[i] = -ve)
*/
if (dnaflag || (gdist <= 0))
{
for (i=0;i<prf_length;i++) gap_pos[i] = gaps[i];
}
else
{
i=0;
while (i<prf_length)
{
if (gaps[i] <= 0)
{
gap_pos[i] = gaps[i];
i++;
}
else
{
for (j = -gdist+1; j<0; j++)
{
if ((i+j>=0) && (i+j<prf_length) &&
((gaps[i+j] == 0) || (gaps[i+j] < j))) gap_pos[i+j] = j;
}
while (gaps[i] > 0)
{
if (i>=prf_length) break;
gap_pos[i] = gaps[i];
i++;
}
for (j = 0; j<gdist; j++)
{
if (gaps[i+j] > 0) break;
if ((i+j>=0) && (i+j<prf_length) &&
((gaps[i+j] == 0) || (gaps[i+j] < -j))) gap_pos[i+j] = -j-1;
}
i += j;
}
}
}
if (debug>1)
{
fprintf(stdout,"gap open %d gap ext %d\n",(pint)gapcoef,(pint)lencoef);
fprintf(stdout,"gaps:\n");
for(i=0;i<prf_length;i++) fprintf(stdout,"%d ", (pint)gaps[i]);
fprintf(stdout,"\n");
fprintf(stdout,"gap_pos:\n");
for(i=0;i<prf_length;i++) fprintf(stdout,"%d ", (pint)gap_pos[i]);
fprintf(stdout,"\n");
}
for (j=0;j<prf_length; j++)
{
if (gap_pos[j] <= 0)
{
/*
apply residue-specific and hydrophilic gap penalties.
*/
if (!dnaflag) {
profile[j+1][GAPCOL] = local_penalty(gapcoef, j,
p_weight, h_weight, v_weight);
profile[j+1][LENCOL] = lencoef;
}
else {
profile[j+1][GAPCOL] = gapcoef;
profile[j+1][LENCOL] = lencoef;
}
/*
increase gap penalty near to existing gaps.
*/
if (gap_pos[j] < 0)
{
profile[j+1][GAPCOL] *= 2.0+2.0*(gdist+gap_pos[j])/gdist;
}
}
else
{
scale = ((float)(numseq-gaps[j])/(float)numseq) * reduced_gap;
profile[j+1][GAPCOL] = scale*gapcoef;
profile[j+1][LENCOL] = 0.5 * lencoef;
}
/*
apply the gap penalty mask
*/
if (struct_penalties != NONE)
{
val = gap_penalty_mask[j]-'0';
if (val > 0 && val < 10)
{
profile[j+1][GAPCOL] *= val;
profile[j+1][LENCOL] *= val;
}
}
/*
make sure no penalty is zero - even for all-gap positions
*/
if (profile[j+1][GAPCOL] <= 0) profile[j+1][GAPCOL] = 1;
if (profile[j+1][LENCOL] <= 0) profile[j+1][LENCOL] = 1;
}
/* set the penalties at the beginning and end of the profile */
if(endgappenalties==TRUE)
{
profile[0][GAPCOL] = gapcoef;
profile[0][LENCOL] = lencoef;
}
else
{
profile[0][GAPCOL] = 0;
profile[0][LENCOL] = 0;
profile[prf_length][GAPCOL] = 0;
profile[prf_length][LENCOL] = 0;
}
if (debug>0)
{
fprintf(stdout,"Opening penalties:\n");
for(i=0;i<=prf_length;i++) fprintf(stdout," %d:%d ",i, (pint)profile[i][GAPCOL]);
fprintf(stdout,"\n");
}
if (debug>0)
{
fprintf(stdout,"Extension penalties:\n");
for(i=0;i<=prf_length;i++) fprintf(stdout,"%d:%d ",i, (pint)profile[i][LENCOL]);
fprintf(stdout,"\n");
}
if ((!dnaflag) && (nvar_pen == FALSE))
v_weight=ckfree((void *)v_weight);
if ((!dnaflag) && (npref_pen == FALSE))
p_weight=ckfree((void *)p_weight);
if ((!dnaflag) && (nhyd_pen == FALSE))
h_weight=ckfree((void *)h_weight);
gap_pos=ckfree((void *)gap_pos);
}
void calc_v_penalties(char **aln, sint n, sint fs, sint ls, sint *weight)
{
char ix1,ix2;
sint i,j,k,t;
for (i=0;i<n;i++)
{
weight[i] = 0;
t=0;
for(j=i-vwindow;j<i+vwindow;j++)
{
if(j>=0 && j<n)
{
ix1 = aln[fs][j];
ix2 = aln[fs+1][j];
if ((ix1 < 0) || (ix1 > max_aa) || (ix2< 0) || (ix2> max_aa)) continue;
weight[i] += vlut[amino_acid_codes[ix1]-'A'][amino_acid_codes[ix2]-'A'];
t++;
}
}
/* now we have a weight -t < w < t */
weight[i] +=t;
if(t>0)
weight[i] = (weight[i]*100)/(2*t);
else
weight[i] = 100;
/* now we have a weight vll < w < 100 */
if (weight[i]<vll) weight[i]=vll;
}
}
void calc_p_penalties(char **aln, sint n, sint fs, sint ls, sint *weight)
{
char ix;
sint j,k,numseq;
sint i;
numseq = ls - fs;
for (i=0;i<n;i++)
{
weight[i] = 0;
for (k=fs;k<ls;k++)
{
for (j=0;j<22;j++)
{
ix = aln[k][i];
if ((ix < 0) || (ix > max_aa)) continue;
if (amino_acid_codes[ix] == pr[j])
{
weight[i] += (180-pas_op[j]);
break;
}
}
}
weight[i] /= numseq;
}
}
void calc_h_penalties(char **aln, sint n, sint fs, sint ls, sint *weight)
{
/*
weight[] is the length of the hydrophilic run of residues.
*/
char ix;
sint nh,j,k;
sint i,e,s;
sint *hyd;
float scale;
hyd = (sint *)ckalloc((n+2) * sizeof(sint));
nh = (sint)strlen(hyd_residues);
for (i=0;i<n;i++)
weight[i] = 0;
for (k=fs;k<ls;k++)
{
for (i=0;i<n;i++)
{
hyd[i] = 0;
for (j=0;j<nh;j++)
{
ix = aln[k][i];
if ((ix < 0) || (ix > max_aa)) continue;
if (amino_acid_codes[ix] == hyd_residues[j])
{
hyd[i] = 1;
break;
}
}
}
i = 0;
while (i < n)
{
if (hyd[i] == 0) i++;
else
{
s = i;
while ((hyd[i] != 0) && (i<n)) i++;
e = i;
if (e-s > 3)
for (j=s; j<e; j++) weight[j] += 100;
}
}
}
scale = ls - fs;
for (i=0;i<n;i++)
weight[i] /= scale;
hyd=ckfree((void *)hyd);
if (debug>1)
{
for(i=0;i<n;i++) fprintf(stdout,"%d ", (pint)weight[i]);
fprintf(stdout,"\n");
}
}
sint local_penalty(sint penalty, sint n, sint *pweight, sint *hweight, sint *vweight)
{
Boolean h = FALSE;
float gw;
if (dnaflag) return(1);
gw = 1.0;
if (nvar_pen == FALSE)
{
gw *= (float)vweight[n]/100.0;
}
if (nhyd_pen == FALSE)
{
if (hweight[n] > 0)
{
gw *= 0.5;
h = TRUE;
}
}
if ((npref_pen == FALSE) && (h==FALSE))
{
gw *= ((float)pweight[n]/100.0);
}
gw *= penalty;
return((sint)gw);
}
float percentid(char *s1, char *s2,sint length)
{
sint i;
sint count,total;
float score;
count = total = 0;
for (i=0;i<length;i++) {
if ((s1[i]>=0) && (s1[i]<max_aa)) {
total++;
if (s1[i] == s2[i]) count++;
}
if (s1[i]==(-3) || s2[i]==(-3)) break;
}
if(total==0) score=0;
else
score = 100.0 * (float)count / (float)total;
return(score);
}
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